New Antibiotic Lolamycin Spares Gut Microbiome While Fighting Infections

The rise of infections caused by Gram-negative pathogens has become a significant public health concern, typically necessitating the use of broad-spectrum antibiotics. These treatments, while effective, often disrupt the gut microbiome, leading to secondary infections and other health complications. Recognizing the urgent need for more selective antibiotics, a new innovative antibiotic, as detailed in a recent study published in Nature, selectively targets Gram-negative bacteria while sparing beneficial gut bacteria. 

Lolamycin, developed by researchers at the University of Illinois Urbana-Champaign, specifically targets the lipoprotein transport system of Gram-negative bacteria. This novel mechanism of action ensures that pathogenic bacteria are effectively eliminated without harming commensal bacteria in the gut. Such selectivity mitigates the risk of secondary infections, such as those caused by Clostridioides difficile, a common and dangerous hospital-associated infection.

The efficacy of lolamycin has been demonstrated across multiple preclinical models. In studies involving over 130 multidrug-resistant clinical isolates, lolamycin showed significant activity. In mouse models of acute pneumonia and septicemia, lolamycin treatment resulted in a 100% survival rate for septicemic mice and a 70% survival rate for those with pneumonia. These promising results underscore the potential of lolamycin to treat severe infections that are resistant to existing antibiotics.

One of the most compelling aspects of lolamycin is its ability to preserve the gut microbiome. Standard antibiotics like amoxicillin and clindamycin often cause dramatic shifts in gut bacterial populations, reducing beneficial microbial groups and increasing susceptibility to secondary infections. In contrast, lolamycin treatment did not cause significant changes in the taxonomic composition of the mouse gut microbiome over a treatment and recovery period. This microbiome-sparing property is vital for reducing the risk of C. difficile colonization and other related complications.

While the discovery of lolamycin is a significant advancement, further research is necessary to bring this antibiotic to clinical use. Extensive testing against a broader range of bacterial strains, detailed toxicology studies, and assessments of resistance development are critical next steps. 

For those interested in learning more about the development and potential of lolamycin, raw sequencing data and analysis scripts have been made available by the researchers. These resources can be accessed at the NCBI Sequence Read Archive and on platforms like GitHub and Zenodo. 


REFERENCES


Muñoz, K.A., Ulrich, R.J., Vasan, A.K. et al. A Gram-negative-selective antibiotic that spares the gut microbiome. Nature (2024). https://doi.org/10.1038/s41586-024-07502-0

A Gram-negative-selective antibiotic that spares the gut microbiome (springer.com)

https://github.com/HPCBio/hergenrother-16S-mouse-2022Sept 

https://zenodo.org/records/10980656

Munoz KA. Development of LolCDE inhibitors as microbiome-sparing gram-negative-selective antibiotics (Doctoral dissertation, University of Illinois at Urbana-Champaign).

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